GOLDEN YELLOW SCJ 1006

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study performed under GLP without deviations

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

92/69/EEC

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: FAT 40543/A
Description: Red powder
Batch: TV RN 196-200
Purity: 90%
Test substance storage conditions: At room temperature in the dark
Stability under storage: Stable
Expiry date: November 01, 2000
Stability in vehicle Water: not indicated

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species: Albino Rabbit, New Zealand White, (SPF-Quality), Source: Broekman Institute, Someren, The Netherlands.
Number of animals: 3 male rabbits
Age at start of treatment: Approx. 7 weeks
Body weight at start of treatment: 1401 - 1510 grams
Identification: Ear tag.
ANIMAL HUSBANDRY
Conditions: Air-conditioned room with approximately 15 air changes per hour and the environment controlled with optimal conditions considered as being a temperature of 21 °C and a relative humidity of 50%. Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity. Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.
Accommodation: Individually in labelled cages with perforated floors (Scanbur Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 gram per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, hay (BMI, Helmond, The Netherlands) was provided once a week.
Water: Free access to tap-water diluted with decalcified water. Certificates of analysis were examined and retained in the NOTOX archives.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: The powdery test substance was moistened with distilled water.

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

terminated after 7 days as all scores were 0.

Number of animals:

3

Details on study design:

Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm ²).
The animals were examined, and the skin to be treated in particular, prior to test substance administration and no abnormalities were detected. On test day 1, 0.5 grams of the test substance was moistened (The 0.5 grams was moistened with 2 ml of distilled water, to obtain a mixture that was suitable for application) and subsequently applied to the intact skin of the clipped area on one flank, using a Scotchpak-non-woven patch (Supplier, 3M, St. Paul, U.S.A.) of 2x3 cm. A similar patch (but without test substance and water) was applied to the contralateral flank, to act as a procedural control. Both patches were mounted on Micropore tape*, which was wrapped around the abdomen and secured with Coban elastic bandage.
Four hours after the application, the dressing was removed and the remaining test substance removed using a tissue moistened with tap-water and subsequently a dry tissue. Whenever considered necessary the skin areas concerned of the animals were re-clipped and/or washed with moistened tissues at least 3 hours before the observations, to facilitate the scoring.
Based on the results obtained in this study and after consultation with the sponsor, the study was repeated. In this repeat, the skin of the rabbits was cleaned by depilation after exposure to the test substance in order to facilitate scoring. This study (NOTOX project 171056) is reported in the Appendix.
OBSERVATIONS
Mortality/Viability: Twice daily
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application).
Irritation : The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 days after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.
The skin reactions were graded according to the following numerical scoring system:
ERYTHEMA AND ESCHAR FORMATION
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness): 4 (In case of signs of necrosis or corrosion (injuries in depth) preventing erythema reading, the maximum grade for erythema (= 4) is given)
OEDEMA FORMATION
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure): 4
INTERPRETATION OF RESULTS
The irritation scores and all other observations were transcribed for compilation and analysis.
The individual scores for erythema and oedema are summarised in tabular form.
A primary irritation index was calculated (the sum of the irritation scores for erythema and oedema obtained at 24 and 72 hours after exposure, divided by 2 times the number of animals used in the study). With the primary irritation index a degree of irritation was obtained, using the table described below (based on Draize et.al. (1944) J.Pharmacol .Exp. 82, 377):
Primary irritation index Degree of irritation
0: non-irritating
> 0 - 0.4: negligibly irritating
>0.4 - 2.0: mildly irritating
>2.0 - 5.0: moderately irritating
>5.0 - 8.0: severely irritating
Note: Where the scoring procedure and the clinical judgement were not in agreement, the assessment of irritancy was based on the latter.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: scoring was hardly possible due to red staining but deduced from the preliminary test in the skin sensitisation study in which the skin was depilated prior to treatment

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: scoring was hardly possible due to red staining but deduced from the preliminary test in the skin sensitisation study in which the skin was depilated prior to treatment

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: scoring was hardly possible due to red staining but deduced from the preliminary test in the skin sensitisation study in which the skin was depilated prior to treatment

Results 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: scoring was hardly possible due to red staining but deduced from the preliminary test in the skin sensitisation study in which the skin was depilated prior to treatment

Results 5

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: 7 days following treatment

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 7

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 8

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 9

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

Due to the absence of available scores for erythema during the first 72 hours of the study, no primary irritation index could be calculated. A repeat of the study, in which the skin was cleaned after exposure to the test substance by depilation, also allowed no conclusion to be drawn, since comparable reactions were observed in the test substance treated skin area and the control site. These reactions were considered to be caused by the depilation procedures. For the sensitisation study with the same substance (NOTOX project 162258), a preliminary irritation test was carried out in guinea pigs. In this test, to remove the staining caused by the test substance and to facilitate scoring, the treated skin was depilated. The results obtained indicate that no irritation was caused by similar concentrations of FAT40543/A after an exposure period of 24 hours. Based on the results obtained in this study and in the preliminary irritation test of the sensitisation study with the same test substance, it is concluded that no irritation is caused by FAT40543/A after 4 hours of exposure. However, red staining of the skin occurred, which persisted for at least 7 days after exposure.

Other effects:

Red staining of the treated skin was observed throughout the 7 day observation period. No oedema were observed. No erythema were observed on day 7.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

FAT40543/A was shown to be non-irritant to rabbit skin. However, red staining of the skin was noted for 7 days.

Executive summary:

The study was carried out in accordance with the OECD guideline No. 404, 'Acute Dermal Irritation/Corrosion' and the EEC Directive 92/69/EEC, B.4, 'Acute Toxicity - Skin irritation.

Three rabbits were exposed to 0.5 grams of FAT40543/A, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7 days after exposure. Exposure to FAT40543/A resulted in red staining of the treated skin, and hence scoring for erythema was made impossible for the first 72 hours after application. No erythema was observed at the observation 7 days after exposure. No oedema was observed during the study. No signs of systemic intoxication were observed during the study period. Due to the absence of available scores for erythema during the first 72 hours of the study, no primary irritation index could be calculated. A repeat of the study, in which the skin was cleaned after exposure to the test substance by depilation, also allowed no conclusion to be drawn, since comparable reactions were observed in the test substance treated skin area and the control site. These reactions were considered to be caused by the depilation procedures. For the sensitisation study with the same substance (NOTOX project 162258), a preliminary irritation test was carried out in guinea pigs. In this test, to remove the staining caused by the test substance and to facilitate scoring, the treated skin was depilated. The results obtained indicate that no irritation was caused by similar concentrations of FAT40543/A after an exposure period of 24 hours. Based on the results obtained in this study and in the preliminary irritation test of the sensitisation study with the same test substance, it is concluded that no irritation is caused by FAT40543/A after 4 hours of exposure. However, red staining of the skin occurred, which persisted for at least 7 days after exposure.

CORROSION: There was no evidence of a corrosive effect on the skin

COLOURATION: Red staining of the treated skin by the test substance was observed.

TOXICITY SYMPTOMS / MORTALITY: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.